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空间转录学揭示了转录学和免疫微环境在甲状腺癌分化过程中的重编程
Kang Ning1,2,3, Bu Zou1,2,3, Yongchao Yu1,2,3
1Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|September 5, 2025
概括
无塑性甲状腺癌 (ATC) 通过基因组变化和免疫抑制从差异化甲状腺癌 (DTC) 演变. 损失的PDCD4驱动瘤相关的巨细胞透,对于ATC的进展至关重要.
科学领域:
- 癌症学
- 基因组学
- 免疫学
背景情况:
- 甲状腺癌 (ATC) 是一种高度致命的恶性瘤.
- 甲状腺癌通常是由差异化甲状腺癌 (DTC) 引起的,原因是人们对甲状腺癌的分化过程不太了解.
研究的目的:
- 阐明推动从DTC到ATC的分子机制.
- 确定甲状腺癌分化中的关键调节者和细胞参与者.
主要方法:
- 在共存的DTC和ATC区域上进行空间转录组测序 (spRNAseq).
- 整体外体测序和推断CNV分析
- 轨迹分析和机械实验.
主要成果:
- ATC表现出高调的免疫抑制,血管生成和ECM重塑基因.
- 邻近的DTC区域显示早期的基因组变化,
- PDCD4和TYMP是甲状腺癌脱差的关键调节剂.
- 瘤相关的巨细胞 (TAMs) 富含ATC,促进免疫抑制.
- 通过eIF4A依赖的途径促进了PDCD4的透.
结论:
- 具有ATC样基因组变化的DTC经历了转录和免疫重编程,成为ATC.
- 由PDCD4损失引起的TAM形成对ATC的发展和进展至关重要.
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